Genetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Bui, T; Stafford, N; Oceandy, D

Genetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Bui, T Stafford, N Oceandy, D

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: CELLS, 2023, 12, (17), pp. 2121
Issue Date:: 2023-09-01

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Field	Value	Language
dc.contributor.author	Bui, T
dc.contributor.author	Stafford, N
dc.contributor.author	Oceandy, D
dc.date.accessioned	2024-05-04T02:10:03Z
dc.date.available	2023-08-17
dc.date.available	2024-05-04T02:10:03Z
dc.date.issued	2023-09-01
dc.identifier.citation	CELLS, 2023, 12, (17), pp. 2121
dc.identifier.issn	2073-4409
dc.identifier.issn	2073-4409
dc.identifier.uri	http://hdl.handle.net/10453/178640
dc.description.abstract	Cardiomyocyte loss following myocardial infarction cannot be addressed with current clinical therapies. Cell therapy with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a potential approach to replace cardiomyocyte loss. However, engraftment rates in pre-clinical studies have been low, highlighting a need to refine current iPSC-CM technology. In this study, we demonstrated that inducing Yes-associated protein (YAP) by genetic and pharmacological approaches resulted in increased iPSC-CM proliferation and reduced apoptosis in response to oxidative stress. Interestingly, iPSC-CM maturation was differently affected by each strategy, with genetic activation of YAP resulting in a more immature cardiomyocyte-like phenotype not witnessed upon pharmacological YAP activation. Overall, we conclude that YAP activation in iPSC-CMs enhances cell survival and proliferative capacity. Therefore, strategies targeting YAP, or its upstream regulator the Hippo signalling pathway, could potentially be used to improve the efficacy of iPSC-CM technology for use as a future regenerative therapy in myocardial infarction.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	CELLS
dc.relation.isbasedon	10.3390/cells12172121
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.mesh	Humans
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Apoptosis
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Humans
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Apoptosis
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Apoptosis
dc.subject.mesh	Myocardial Infarction
dc.subject.mesh	Cell Proliferation
dc.title	Genetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access	*
dc.date.updated	2024-05-04T02:09:56Z
pubs.issue	17
pubs.publication-status	Published online
pubs.volume	12
utslib.citation.issue	17

Abstract:

Cardiomyocyte loss following myocardial infarction cannot be addressed with current clinical therapies. Cell therapy with induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a potential approach to replace cardiomyocyte loss. However, engraftment rates in pre-clinical studies have been low, highlighting a need to refine current iPSC-CM technology. In this study, we demonstrated that inducing Yes-associated protein (YAP) by genetic and pharmacological approaches resulted in increased iPSC-CM proliferation and reduced apoptosis in response to oxidative stress. Interestingly, iPSC-CM maturation was differently affected by each strategy, with genetic activation of YAP resulting in a more immature cardiomyocyte-like phenotype not witnessed upon pharmacological YAP activation. Overall, we conclude that YAP activation in iPSC-CMs enhances cell survival and proliferative capacity. Therefore, strategies targeting YAP, or its upstream regulator the Hippo signalling pathway, could potentially be used to improve the efficacy of iPSC-CM technology for use as a future regenerative therapy in myocardial infarction.

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http://hdl.handle.net/10453/178640